Quantitative assessment of the first acute rejection as a predictor of renal transplant outcome

Background. Acute rejection (AR) of the transplanted kidney has been identi fied as the major risk factor for the development of chronic rejection and immunological graft loss. However, the clinical presentation and response t o AR therapy can vary considerably between recipients. Methods. We studied the first AR episode in 201 kidney-only recipients tran splanted between January 1987 and June 1998 who were biopsied between April 1993 and June 1998 and were graded using the Banff schema. All patients re ceived cyclosporine-based immunosuppression. There were 134 cadaver donor ( 66.7%) and 67 live donor (33.3%) recipients followed for a mean of 46.2 (ra nge 4-128) months, All Banff grade 1-3 and 40/78 borderline (BL) cases were treated for rejection after biopsy. These patients were compared with a co ntemporaneous control population who did not experience AR. Demographic ris k factors associated with graft loss were identified in both univariate and multivariate analysis. Daily (0-18) serum creatinine (SCr) values during a nd after the AR were plotted for each patient to generate curves and calcul ate area under the serum creatinine versus time curve (mg/dl/day). Four res ponse patterns to treatment were identified according to the velocity of % increase (V1) and decrease (V2) of serum creatinine, These were identified as rapid rise and fall (n=62); rapid rise and slow fall (n=43); slow rise a nd fall (n=55); and dow rise and rapid fall (n=41). Kaplan-Meier graft surv ivals were compared between the groups. Results. Any Banff grade was associated with increased risk for graft loss (P=0.0001). However, no significant differences were observed between the B anff BL and B1-3 groups, or among those BL patients who were treated or rem ained untreated for AR. Multivariate analysis identified a black recipient (P=0.03, risk ratio 2.0) and area under the serum creatinine versus time cu rve (P=0.0001, risk ratio 3.2) as significant risk factors for graft loss. The AR response pattern RS resulted in a significantly (P=0.0072) diminishe d 5-year graft survival (45%) compared with the other groups. Serum creatin ine pattern, but not Banff grade, was also a significant (P=0.025) predicto r of re-rejection. Conclusions. These data suggest that all Banff grades,including BL, carry a significant risk for graft loss,: and the initial response to antirejectio n therapy can predict long-term graft outcome. They support the practice of treating AR promptly and definitively and suggest that the RS subgroup of rejecting grafts could be targeted for additional antirejection therapy. Th is subgroup can be identified by 10 days of AR therapy, and should be the s ubject of further study.